Specific mechanisms of how the reactive microenvironment affects prostate cancer progression are[unreadable] unknown. Previous studies from our group have shown that the reactive microenvironment has properties[unreadable] and gene expression similar to wound repair biology. These include changes in stromal cell phenotype,[unreadable] altered neurogenesis and the involvement of specific T regulatory cells. We have also shown that reactive[unreadable] stroma is tumor promoting. These studies have shown that carcinoma cells and nerves exhibit reciprocal[unreadable] interactions leading to elevated carcinoma proliferation and induced neurogenesis. In addition, the[unreadable] involvement of gamma-sigma T regulatory cells may play an important role in tumor progression. The concurrent[unreadable] recruitment of myofibroblasts to PIN and carcinoma foci implicates a coordinated host response in these[unreadable] biologies that promotes tumorigenesis. Importantly, our group has shown that specific biomarkers of this[unreadable] reactive microenvironment are predictive of recurrence of human prostate cancer. The integrated biologies[unreadable] of this response and specific mechanisms are not yet understood at a level where more effective prognostics[unreadable] or novel therapeutics can be developed. Accordingly, the overall objectives of this project are to understand[unreadable] how reactive stroma, neurogenesis, and immunity responses in prostate cancer microenvironment function[unreadable] and interact mechanistically during the initiation and progression of early, organ confined disease. The[unreadable] endpoint of this study is to understand the key components, regulators, and mechanisms with a specific[unreadable] focus on early prostate cancer. We have assembled a team of experts who will focus their efforts on[unreadable] understanding three interrelated biologies in the tumor microenvironment. We propose a Program[unreadable] composed of an Expression Analysis and Pathology Core and three interrelated Projects. Project 1 will[unreadable] address the co-evolution, origin, and specific regulators of reactive stromal cells. Project .2 will address the[unreadable] role of axonogenesis and neurogenesis in regulating early cancer. Project 3 will focus on the role of gamma-sigma T[unreadable] regulatory cells and signaling through Toll-like receptors in prostate cancer progression. Together, these[unreadable] Projects and Core will provide fundamental data regarding the temporal and spatial composition, gene[unreadable] expression profiling, and potential regulators of the microenvironment in human tissues and mouse models.[unreadable] This group of Investigators has worked together for several years and has planned these studies around[unreadable] their pre-established collaborations. The overall goal of this Program is to provide novel pre-clinical data,[unreadable] from which more effective biomarkers and therapeutics can be developed that target the microenvironment[unreadable] of early prostate cancer.[unreadable] PERFORMANCE SITE(S) (organization, city, state)[unreadable] Baylor College of Medicine[unreadable] Houston Texas[unreadable] PHS 398 (Rev. 04/06) Page 2 Form Page 2[unreadable] Principal Investigator/Program Director (Last, First, Middle): Rowley, David R., Ph.D.[unreadable] KEY PERSONNEL. See instructions. Use continuation pages as needed to provide the required information in the format shown below.[unreadable] Start with Principal Investigator(s). List all other key personnel in alphabetical order, last name first.[unreadable] Name[unreadable] Rowley, David R,[unreadable] Rowley, David R.[unreadable] Abd-EI-Fatta, ElMoataz[unreadable] Ayala, Gustavo E.[unreadable] Ayala, Gustavo E.[unreadable] Chen, Wenhao (July, 2006)[unreadable] Dai, Hong[unreadable] Hilsenbeck, Susan G.[unreadable] Hong, Jun (July 2006)[unreadable] Ittman, Michael M.[unreadable] Ittman, Michael M.[unreadable] eRA Commons User Name[unreadable] DROWLEY[unreadable] DROWLEY[unreadable] GAYALA[unreadable] GAYALA[unreadable] Shilsenbeck[unreadable] Ittmann[unreadable] Ittmann[unreadable] Organization[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Baylor College of Med.[unreadable] Role on Project[unreadable] Principal Investigator[unreadable] Project Leader, P1[unreadable] Research Associate, P2[unreadable] Project Leader, P2[unreadable] CORE Co-Leader[unreadable] Postdoctoral Fellow, P3[unreadable] Research Associate, P2[unreadable] Co-Investigator, CORE[unreadable] Postdoctoral Fellow, P3[unreadable] CORE Leader[unreadable] Collaborator, P2[unreadable] OTHER SIGNIFICANT CONTRIBUTORS[unreadable] Name[unreadable] NA[unreadable] Organization Role on Project